Glutathione disulfide enhances the reduced glutathione inhibition of lipid peroxidation in rat liver microsomes.
Experiments were undertaken to examine the effects of reduced (GSH) and oxidized (GSSG) glutathione on lipid peroxidation of rat liver microsomes. Dependence on microsomal alpha-tocopherol was shown for the GSH inhibition of lipid peroxidation. However, when GSH (5 mM) and GSSG (2.5 mM) were combined in the assay system, inhibition of lipid peroxidation was enhanced markedly over that with GSH alone in microsomes containing alpha-tocopherol. Surprisingly, the synergistic inhibitory effect of GSH and GSSG was also observed for microsomes that were deficient in alpha-tocopherol. These data suggest that there may be more than one factor responsible for the glutathione-dependent inhibition of lipid peroxidation. The first is dependent upon microsomal alpha-tocopherol and likely requires GSH for alpha-tocopherol regeneration from the alpha-tocopheroxyl radical during lipid peroxidation. The second factor appears to be independent of alpha-tocopherol and may involve the reduction of lipid hydroperoxides to their corresponding alcohols. One, or possibly both, of these factors may be activated by GSSG through thiol/disulfide exchange with a protein sulfhydryl moiety.
Scholz
R W
RW
Environmental Resources Research Institute, Pennsylvania State University, University Park 16802.
Graham
K S
KS
Reddy
C C
CC
D000818:Animals; D005978:Glutathione / Q000494:pharmacology*; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013329:Structure-Activity Relationship; D014810:Vitamin E / Q000378:metabolism
D008054:Lipid Peroxides; D014810:Vitamin E; D009249:NADP; D005978:Glutathione